NOX-A12 Plus Radiotherapy and Bevacizumab Produces Responses in Previously Untreated Glioblastoma

The addition of the CXCL12 inhibitor NOX-A12 to standard-of-care (SOC) radiotherapy and bevacizumab (Avastin) elicited responses when used as first-line treatment in patients with glioblastoma, according to updated data from the expansion arm of the phase 1/2 GLORIA trial (NCT04121455).¹

Among 6 evaluable patients in the expansion arm, 1 patient experienced a complete response (CR) after previously having a best response of 89.9% tumor shrinkage. Furthermore, 2 patients achieved more than 99% tumor shrinkage, resulting in a CR or near-CR rate of 50%.

“We are very pleased to report this highly positive update from the expansion arm of our GLORIA clinical trial evaluating our lead asset NOX-A12 in combination with radiotherapy and bevacizumab in glioblastoma,” Aram Mangasarian, chief executive officer of TME Pharma, stated in a news release. “It is very encouraging to see 1 patient achieve no detectable tumor and 2 patients coming extremely close to CR, achieving a reduction in tumor size of more than 99%. This CR took about 12 months of therapy to achieve, underlining the importance of mature data to fully evaluate the power of NOX-A12-based therapy.”

Previously reported data from the expansion arm showed that at a median of 15 months on the study, 5 of 6 patients (83%) were still alive.² Moreover, 5 of 6 patients achieved durable partial responses per modified Response Assessment in Neuro-Oncology criteria, and 1 patient experienced progressive disease due to distant failure despite maintained target lesion control.³

The single-arm GLORIA trial enrolled patients who were at least 18 years of age with newly diagnosed stage IV glioblastoma of unmethylated methylguanine methyl transferase (MGMT) promoter status who were either not amenable to resection or who had incomplete tumor resection.⁴ Patients were also required to have an ECOG performance status of 0 to 2 and an estimated life expectancy of at least 3 months. Patients needed to be receiving a stable or decreasing dose of corticosteroids in the week prior to enrollment.

Key exclusion criteria included having chemotherapy within the past 5 years; a history of other cancers other than adequately treated basal or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the patient was disease free for at least 5 years; clinically significant or uncontrolled cardiovascular disease; or prior radiotherapy to the head.

In the expansion arm, patients received 600 mg of NOX-A12 per week plus 10 mg/kg of bevacizumab every 2 weeks for 26 weeks. Patients were also given radiotherapy at a cumulative dose of 60 Gy in 2-Gy fractions during weeks 1 to 6. An additional expansion arm is evaluating the same dosing of NOX-A12 and radiotherapy in combination with pembrolizumab (Keytruda) given at 200 mg once every 3 weeks for 26 weeks.

Safety served as the trial’s primary end point. Secondary end points include progression-free survival, overall survival, tumor vascularization, quality of life, and neurologic functions.

“Taken together with the promising picture emerging from our survival data, it is becoming clearer that NOX-A12 used in this treatment combination can provide clinically meaningful benefit over SOC for [patients with] brain cancer, who currently have such limited therapeutic options,” Mangasarian added in the news release.¹

Previously reported data showed the triple combination was well tolerated, and no dose-limiting toxicities were observed.³

References

1. TME Pharma provides positive data update on best response to therapy with first complete response in GLORIA trial in Glioblastoma, bringing 50% of patients in expansion arm to complete or near-complete response. News release. TME Pharma. July 13, 2023. Accessed July 17, 2023. https://www.tmepharma.com/downloads/pressrel/2023-07-13_TME_GLORIA_CR_update_EN.pdf
2. TME Pharma announces positive 15-month survival data from GLORIA expansion arm evaluating NOX-A12 in combination with radiotherapy and bevacizumab in glioblastoma. News release. TME Pharma. June 28, 2023. Accessed July 17, 2023. https://www.tmepharma.com/downloads/pressrel/2023-06-28_TME_GLORIA_15-Month_Survival_Update_EN.pdf
3. Positive updated interim results from NOX-A12 GLORIA phase 1/2 in brain cancer presented at the Society for Neuro-Oncology 2022 Annual Meeting. News release. TME Pharma. November 19, 2022. Accessed July 17, 2023. https://www.tmepharma.com/downloads/pressrel/2022-11-19_TME_Pharma_SNO_Poster_EN.pdf
4. Glioblastoma treatment with irradiation and olaptesed pegol (NOX-A12) in MGMT unmethylated patients (GLORIA). ClinicalTrials.gov. Updated June 22, 2023. Accessed July 17, 2023. https://clinicaltrials.gov/study/NCT04121455